A role for the unfolded protein response (UPR) in virulence and antifungal susceptibility in Aspergillus fumigatus.

PLoS Pathogens
Daryl L RichieDavid S Askew

Abstract

Filamentous fungi rely heavily on the secretory pathway, both for the delivery of cell wall components to the hyphal tip and the production and secretion of extracellular hydrolytic enzymes needed to support growth on polymeric substrates. Increased demand on the secretory system exerts stress on the endoplasmic reticulum (ER), which is countered by the activation of a coordinated stress response pathway termed the unfolded protein response (UPR). To determine the contribution of the UPR to the growth and virulence of the filamentous fungal pathogen Aspergillus fumigatus, we disrupted the hacA gene, encoding the major transcriptional regulator of the UPR. The DeltahacA mutant was unable to activate the UPR in response to ER stress and was hypersensitive to agents that disrupt ER homeostasis or the cell wall. Failure to induce the UPR did not affect radial growth on rich medium at 37 degrees C, but cell wall integrity was disrupted at 45 degrees C, resulting in a dramatic loss in viability. The DeltahacA mutant displayed a reduced capacity for protease secretion and was growth-impaired when challenged to assimilate nutrients from complex substrates. In addition, the DeltahacA mutant exhibited increased susceptibility to current ...Continue Reading

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Jul 9, 2014·Annual Review of Phytopathology·Christian P KubicekN Louise Glass
Nov 25, 2014·Fungal Biology Reviews·Karthik Krishnan, David S Askew
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Feb 8, 2014·Virulence·Seon Ah CheonHyun Ah Kang

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Datasets Mentioned

BETA
EU877964

Methods Mentioned

BETA
protein folding
thermal stress
PCR
genotyping
restriction digest
electrophoresis

Software Mentioned

Etest
Sigma Stat
DNAMAN
CLUSTALW

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